Impact of taxane-based chemotherapeutics on male reproductive function

Lay summary Men and boys with cancer treated with chemotherapy are known to have reduced fertility following their treatment. This is because some chemotherapy drugs can damage the cells in the testicles that make sperm. This study found there is limited information available on the effect of one group of chemotherapy drugs, called taxanes, on testicular function and fertility. More studies are needed to aid clinicians in advising patients on how this taxane-based chemotherapy may affect their future fertility.

Chemotherapy exposure may reduce fertility in males. Adult men may cryopreserve sperm prior to commencing cancer therapy; however, for pre-pubertal males who do not produce sperm, fertility preservation remains experimental. At present, no human has ever been born from cryopreserved pre-pubertal testis tissue, with the most recent breakthrough in this area being the birth of a Rhesus Macaque following autologous transplant of cryopreserved pre-pubertal testis tissue (Fayomi et al. 2019). Current clinical practice on male prepubertal fertility preservation varies globally in terms of eligibility for tissue cryopreservation, methods and duration of storage, future clinical use, and consensus on the assessment of tissue function and reproductive outcomes.
Although numerous chemotherapeutics are used to treat cancers, the impact of different agents on reproductive function and fertility is poorly understood. Taxane-based chemotherapeutics are used to treat numerous cancers; however, robust data on their impact on male fertility is lacking. We reviewed the literature on the effects of taxanebased chemotherapy in male patients on subsequent gonadal function and fertility.
We systematically searched PubMed and Scopus using a previously published methodology (Tian et al. 2020) and registered our protocol (PROSPERO-CRD42021296306). The search terms used in this review are outlined in Supplementary Table 1 (see section on supplementary materials given at the end of this article). We included studies reporting the effects of taxane-based chemotherapy on testicular development and function using PRISMA guidelines. We identified 458 studies, of which 87 were assessed for eligibility (Supplementary Table 2). Five studies met inclusion criteria ( Fig. 1) and involved 512 patients, with 94 eligible for this review (male patients receiving taxanes), and the characteristics of these studies can be found in Table 1.

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Two studies (Pectasides et al. 2009, Chatzidarellis et al. 2010) specifically reported reproductive outcomes in patients who received taxane chemotherapy with all patients (n = 70) in these studies receiving paclitaxel and additional chemotherapy, and neither study included a control group.
Chatzidarellis et al. reported 40 male patients (aged 28 and 60 years) receiving paclitaxel or docetaxel; identifying a significant reduction in inhibin B, an increase in follicle-stimulating hormone (FSH), and a decrease in bilateral testicular volume, with no significant change in luteinizing hormone (LH)    Pectasides et al. report on 30 male patients (aged 17-62 years) treated with paclitaxel, methotrexate, ifosfamide, and cisplatin for poor-risk non-seminoma germ cell tumours; outcome measures were available for 21 patients. Serum FSH levels were significantly elevated 12 months after treatment completion; however, they returned to normal levels at 18 months post-treatment. LH and testosterone levels were unaffected. Overall, 17/21 (80.9%) patients demonstrated recovery of spermatogenesis post-treatment, and a total of 5 patients had gone on to father children.
For the remaining three studies, 24/442 patients received taxane chemotherapy. However, no studies report outcomes of individual patients or stratified by treatment received (Strasser et al. 2006, Burney et al. 2012, Rothermundt et al. 2018. Limited data are available on taxane-based chemotherapy and reproductive outcomes, with no data available for prepubertal males. The single study reporting on spermatogenesis showed that sperm production resumed in the majority of patients (Pectasides et al. 2009), while studies reporting endocrine function post-taxane treatment demonstrated elevated FSH (Pectasides et al. 2009, Chatzidarellis et al. 2010) and reduced inhibin-B (Chatzidarellis et al. 2010). The impact of specific dosing regimens or duration of treatment on reproductive outcomes could not be determined. Prospective data collection on endocrine function, semen analysis, and fatherhood for males receiving taxane-based chemotherapy is required in order to inform clinicians when counselling patients receiving these chemotherapeutics on their future fertility. Given the experimental nature of fertility preservation for pre-pubertal males, the importance of understanding how taxane-based chemotherapy can impact future fertility cannot be understated.